Zalicus Awaits Day of Reckoning, Braces For Key Pain Drug Results

Like any biotech about to release data from a key trial, Zalicus (NASDAQ: ZLCS) is at a crossroads.

Imminently, Cambridge, MA-based Zalicus will publish the top-line numbers from two mid-stage clinical trials of an experimental pain drug called Z160. The stakes are big for Zalicus, because this is its best shot to show investors—or a potential partner—that it possesses what could be a very valuable drug. Should these studies both hit, Zalicus will have options. If they fail, Zalicus will probably have to look at a very different set of choices—the dreaded “strategic” ones. A result in the middle, of course, will leave Zalicus somewhere in-between.

“We’re really on the eve of what has been, for me, a nine-year journey of trying to understand whether this candidate is going to have a clinical benefit,” says Zalicus president and CEO Mark Corrigan. “We are literally waiting on pins and needles.”

Z160 is a reformulated version of a drug that Zalicus’ predecessor, Vancouver, BC-based Neuromed, licensed to Merck several years ago. The old drug fizzled in clinical studies. Corrigan says that this was because of “lousy” pharmaceutical properties, like the fact that it was highly insoluble, which made it difficult for the body to absorb properly. Merck abandoned it, and handed it back to the company, which says it has ironed out those pharmacokinetic issues enough to move it into clinical trials.

Mark Corrigan, president and CEO of Zalicus

The drug candidate is what’s known as a neural-type, or N-type, calcium channel blocker. Without the jargon, what that means is this: N-type calcium channels are proteins that open holes into nerve cells, enabling calcium to be transported inside of those cells. These nerve cells can use calcium ions to communicate with each other, sending out signals, such as pain, to the brain. The scientific theory, then, was by blocking these types of calcium channels, a drug could stop a pain signal from being transmitted. That approach was validated when the FDA approved Jazz Pharmaceuticals’ ziconotide (Prialt) in 2004. Ziconotide blocks a specific type of calcium channel called Cav. 2.2 to help relieve chronic pain.

Z160 is designed to work in the same type of way, with two key differences. Ziconotide is injected directly into a patient’s spinal cord, whereas Z160 is a pill. And Z160 is supposed to bind to and block Cav. 2.2 in a “state-dependent” way—only when these neurons are excited, firing rapidly, and shouting out their pain signals, rather than all the time, Corrigan says.

This is Zalicus’ value proposition: it hopes that this selectivity will translate into the same type of pain killing power as opioids, ziconotide, or neuropathic pain drugs like pregabalin (Lyrica, sold by Pfizer) and duloxetine (Cymbalta, Eli Lilly), without the addictive properties of opioids or the sleepiness, dizziness, or other side effects that have been associated with pregabalin. Or, say, some of the serious side effects like psychosis associated with ziconotide. To date, mild nausea has been the worst side effect reported by some of the 400 or so patients dosed with Z160, according to Corrigan.

Zalicus hopes that Z160 could be an option for people who aren’t responding to these other drugs, and that it could be taken instead of, or in tandem with, these treatments.

“The opportunity to offer, ‘Hey, here is a different way you could begin to assuage the pain,’ is extremely important,” Corrigan says. “There hasn’t really been a new mechanism of action involved in the treatment of pain in 30 years.”

Of course, Zalicus doesn’t have the sizeable data to prove any of this as of yet, which is why the upcoming trials are so important to its future. These trials are … Next Page »